Correlation between Human Immunodeficiency Virus Type 1 RNA Levels in the Female Genital Tract and Immune Activation Associated with Ulceration of the Cervix

Authors:
  • JWJr. Thomas C. Wright
    Jr. Thomas C. Wright
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Abstract
To address the hypothesis that local immune activation resulting from genital ulceration enhances human immunodeficiency virus type 1 (HIV-1) replication and shedding into the genital tract, paired plasma and cervicovaginal lavage (CVL) samples were obtained from 12 HIV-infected women before and after treatment of cervical intraepithelial lesions. Two weeks after treatment, inflammation and ulceration of the cervix were accompanied by major increases in mean concentrations of HIV-1 RNA (200-fold), tumor necrosis factor-α, interleukin 6, and soluble markers shed by activated lymphocytes and macrophages (sCD25 and sCD14, respectively) in CVL samples (P < .01 for each), but not plasma. Strong temporal and quantitative correlations were observed between concentrations of immunological markers and HIV-1 load in this compartment during a 10-week follow-up. Furthermore, in the presence of genital ulceration, HIV-1 in CVL samples was more readily captured by antibodies directed against virion-associated HLA-DR, a marker of host-cell activation, compared with virus in plasma. We suggest that local immune activation increases HIV-1 load in genital secretions, potentially increasing the risk of HIV-1 transmission.